Project Abstract/Summary Cardiac resynchronization therapy (CRT) is a proven treatment for patients with impaired LV function and a wide QRS complex. However, approximately 1/3 of patients do not respond to CRT because of suboptimal LV lead placement yielding persistent dyssynchrony. No large clinical trials have demonstrated that image derived parameters can differentiate responders from non-responders. Significant intra-observer and inter-vendor differences in parameters derived from echocardiography have stimulated the search for alternative imaging methods. We and others have demonstrated that cardiac MRI is an excellent method for measuring mechanical dyssynchrony and identifying regions of scar through late gadolinium enhancement; hence, MRI could possibly guide LV lead placement to avoid non-viable tissue and target regions of late mechanical activation. Unfortunately, a large number of patients considered for CRT have existing pacing systems, or do not have access to advanced MRI laboratories, severely limiting the possibility of MR guidance. The solution: Our recent development of a novel high resolution LV function mapping technique called SQUEEZ now allows us to identify viable LV pacing targets from 4DCT data with a single heartbeat exam. However, the accuracy and precision of 4DCT for measuring dyssynchrony in the LV is unknown and it is clear that motion artifacts in 4DCT may compromise temporal measurements if left uncorrected. In order to achieve the best temporal resolution possible, we propose a novel motion correction scheme called ?ResyncCT? which reduces the motion artifacts generated by CT gantry rotation. Our preliminary results lead us to the following hypothesis: the analysis of ?ResyncCT? motion-corrected 4DCT images with SQUEEZ can be used to target optimal pacing sites to correct LV dyssynchrony with CRT. In order to validate this hypothesis, we will optimize cardiac cine 4DCT acquisitions and ResyncCT motion compensated reconstruction for measuring LV dyssynchrony, and we will optimize and validate SQUEEZ in highly realistic anthropomorphic 3D printed phantoms and in CRT patients. Ultimately, our accuracy in predicting response to CRT will be tested retrospectively in a series of CRT patients in whom 4DCT data was obtained prior to their CRT procedure. For each patient, by analyzing their 4DCT data after ResyncCT and SQUEEZ processing, we will compute a novel ?Lead Placement Score? at the site of their LV lead. We will test the hypothesis that the Lead Placement Score is significantly different in the patients who respond (decrease in End-Systolic Volume > 15% at 6 months) than in those patients who do not respond to CRT.